Figure 2. Subunit structure and regulation of AMPK.

(A) Structure of AMPK. Schematic representation of AMPK highlighting important regions within each of its 3 subunits, as described in the main text (adapted from ref. 64). AID, autoinhibitory domain; CBM, carbohydrate-binding module; CBS, cystathionine-β synthase. (B) Regulation of AMPK. LKB1 and CaMKKβ activate AMPK by phosphorylation of threonine 172 (T172) within the kinase domain of the α subunit. AMPK is returned to an inactive form by dephosphorylation catalyzed by the action of protein phosphatases (PPase). Binding of ADP and AMP to the γ subunit of AMPK protects against dephosphorylation, maintaining the kinase in an active conformation, although recent studies suggest that ADP is likely to be the important physiological regulator of this process. ADP and AMP have also been reported to promote LKB1-mediated phosphorylation of AMPK, whereas calcium directly activates CaMKKβ. In addition, AMP causes a modest allosteric activation of AMPK. Finally, glycogen (and branched-chain carbohydrates) bind to the glycogen-binding domain within the β subunit, allosterically inhibiting AMPK. P, phosphorylation of T172.